Levosimendan Versus Milrinone for Inotropic Support in Pediatric Cardiac Surgery: Results From a Randomized Trial.

OBJECTIVE The present study aimed to determine the differential effects of intraoperative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was used for myocardial function evaluation using biventricular longitudinal strain with 2-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. DESIGN A secondary analysis of a randomized, prospective, double-blinded clinical drug trial. SETTING Two pediatric tertiary university hospitals. PARTICIPANTS Infants between 1 and 12 months old diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. INTERVENTIONS The patients were randomly assigned to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. MEASUREMENTS AND MAIN RESULTS Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning, and before hospital discharge. The association between perioperative parameters and postoperative myocardial function also was investigated. Images were analyzed for left ventricular (n = 67) and right ventricular (n = 44) function. The day after surgery, left ventricular longitudinal strain deteriorated in both the milrinone and levosimendan groups (33% and 39%, respectively). The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (nonsignificant difference). For both groups, biventricular longitudinal strain approached preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day 1 (p = 0.014). CONCLUSIONS Levosimendan was comparable with milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.

[1]  S. Ricksten,et al.  The Effect of Levosimendan Versus Milrinone on the Occurrence Rate of Acute Kidney Injury Following Congenital Heart Surgery in Infants: A Randomized Clinical Trial. , 2019, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[2]  S. Ricksten,et al.  Inotropic and lusitropic effects of levosimendan and milrinone assessed by strain echocardiography—A randomised trial , 2018, Acta anaesthesiologica Scandinavica.

[3]  P. Neuvonen,et al.  Stress-Dose Corticosteroid Versus Placebo in Neonatal Cardiac Operations: A Randomized Controlled Trial. , 2017, The Annals of thoracic surgery.

[4]  T. Ojala,et al.  Velocity vector imaging shows normal cardiac systolic function in survivors of severe bronchopulmonary dysplasia at six to 16 years of age , 2017, Acta paediatrica.

[5]  P. Acar,et al.  Two-dimensional right ventricular strain by speckle tracking for assessment of longitudinal right ventricular function after paediatric congenital heart disease surgery. , 2017, Archives of cardiovascular diseases.

[6]  N. Blom,et al.  Decreased biventricular longitudinal strain shortly after congenital heart defect surgery , 2017, Echocardiography.

[7]  J. Thambo,et al.  Postoperative assessment of left ventricular function by two-dimensional strain (speckle tracking) after paediatric cardiac surgery. , 2016, Archives of cardiovascular diseases.

[8]  F. Dallaire,et al.  Pediatric Reference Values and Z Score Equations for Left Ventricular Systolic Strain Measured by Two-Dimensional Speckle-Tracking Echocardiography. , 2016, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[9]  R. Pignatelli,et al.  Strain Imaging: The Emergence of Speckle Tracking Echocardiography into Clinical Pediatric Cardiology. , 2016, Congenital heart disease.

[10]  F. Roldán,et al.  Left ventricular longitudinal strain measured by speckle tracking as a predictor of the decrease in left ventricular deformation in children with congenital stenosis of the aorta or coarctation of the aorta. , 2013, Ultrasound in medicine & biology.

[11]  P. Rehak,et al.  Levosimendan versus milrinone in neonates and infants after corrective open-heart surgery: A pilot study , 2012, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[12]  R. Ross The Ross Classification for Heart Failure in Children After 25 Years: A Review and an Age-Stratified Revision , 2012, Pediatric Cardiology.

[13]  A. Poncelet,et al.  Congenital Cardiac Surgery : A Randomized , Double-Blind Clinical Trial , 2011 .

[14]  R. Ohye,et al.  Vasoactive–inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass* , 2010, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[15]  F. Carmona,et al.  Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I. , 2008, Cytokine.

[16]  M Pozzi,et al.  The Aristotle score: a complexity-adjusted method to evaluate surgical results. , 2004, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[17]  D. Nelson,et al.  Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease , 2003, Circulation.

[18]  K. Gauvreau,et al.  Center-specific differences in mortality: preliminary analyses using the Risk Adjustment in Congenital Heart Surgery (RACHS-1) method. , 2002, The Journal of thoracic and cardiovascular surgery.

[19]  B. Reichart,et al.  Effect of cardiopulmonary bypass on myocardial function, damage and inflammation after cardiac surgery in newborns and children. , 2001, The Thoracic and cardiovascular surgeon.

[20]  J. Mayer,et al.  Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. , 1995, Circulation.

[21]  S. Di Bernardo,et al.  Use of Levosimendan in Postoperative Setting After Surgical Repair of Congenital Heart Disease in Children , 2017, Pediatric Cardiology.

[22]  F. Cabañas,et al.  Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery , 2013, Pediatric Research.